Selected article for: "activity study and lung disease"
Author: Krämer, Benjamin; Knoll, Rainer; Bonaguro, Lorenzo; ToVinh, Michael; Raabe, Jan; Astaburuaga-García, Rosario; Schulte-Schrepping, Jonas; Kaiser, Kim Melanie; Rieke, Gereon J.; Bischoff, Jenny; Monin, Malte B.; Hoffmeister, Christoph; Schlabe, Stefan; De Domenico, Elena; Reusch, Nico; Händler, Kristian; Reynolds, Gary; Blüthgen, Nils; Hack, Gudrun; Finnemann, Claudia; Nischalke, Hans D.; Strassburg, Christian P.; Stephenson, Emily; Su, Yapeng; Gardner, Louis; Yuan, Dan; Chen, Daniel; Goldman, Jason; Rosenstiel, Philipp; Schmidt, Susanne V.; Latz, Eicke; Hrusovsky, Kevin; Ball, Andrew J.; Johnson, Joe M.; Koenig, Paul-Albert; Schmidt, Florian I.; Haniffa, Muzlifah; Heath, James R.; Kümmerer, Beate M.; Keitel, Verena; Jensen, Björn; Stubbemann, Paula; Kurth, Florian; Sander, Leif E.; Sawitzki, Birgit; Aschenbrenner, Anna C.; Schultze, Joachim L.; Nattermann, Jacob
Title: Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19
  • Cord-id: jcf0045k
  • Document date: 2021_9_4
    • ID: jcf0045k
    Snippet: Longitudinal analyses of the innate immune system including earliest time points are essential to understand the immunopathogenesis and clinical course of COVID-19. Here, we performed a detailed characterization of natural killer cells in 205 patients (403 samples, day 2-41 after symptom onset) from four independent cohorts using single-cell transcriptomics and proteomics together with functional studies. We found elevated IFN-α plasma levels in early severe COVD-19 alongside increased NK cell
    Document: Longitudinal analyses of the innate immune system including earliest time points are essential to understand the immunopathogenesis and clinical course of COVID-19. Here, we performed a detailed characterization of natural killer cells in 205 patients (403 samples, day 2-41 after symptom onset) from four independent cohorts using single-cell transcriptomics and proteomics together with functional studies. We found elevated IFN-α plasma levels in early severe COVD-19 alongside increased NK cell expression of ISGs and genes involved in IFN-α signaling, while upregulation of TNF-induced genes was observed in moderate disease. NK cells exert anti-SARS-CoV-2 activity but are functionally impaired in severe COVID-19. Further, NK cell dysfunction may be relevant for development of fibrotic lung disease in severe COVID-19, as NK cells exhibited impaired anti-fibrotic activity. Our study indicates preferential IFN-α and TNF responses in severe and moderate COVID-19, respectively, and associates prolonged IFN-α-induced NK cell response with poorer disease outcome.

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